Sex Differences in Extinction and Reinstatement of Nicotine Discrimination in Rats: The Effects of Reinforcer Devaluation

Nicotine functions effectively as an interoceptive operant discriminative stimulus (SD) that sets the occasion for voluntarily emitted behavior to be reinforced by biologically relevant outcomes (e.g., food). This has been demonstrated primarily with male rats. Far less is known about nicotine's operant SD functions in female rats. There are no reports of sex differences in extinction and recovery of the SD functions of nicotine, which may elucidate smoking cessation and relapse. In view of this, eight male and eight female rats were trained to nose poke differentially among quasirandomly intermixed sessions of food reinforcement variable interval (VI-30 s) and nonreinforcement in a go/no-go across session one-manipulanda operant drug discrimination procedure. For half the rats, presession administration of nicotine (0.30 mg/kg, subcutaneous) occasioned reinforcement sessions of nose pokes (i.e., SD); for the remaining rats, it occasioned nonreinforcement (S Delta). Saline sessions occasioned the opposite contingencies. Training was conducted first under feeding restriction and then under free feeding, which was then followed by extinction sessions that were also conducted with free feeding. During discrimination training, response rates for females did not differ from males when conducted under restricted feeding but did so during training and later extinction conducted under free feeding. Females also exhibited greater reinstatement of responding under the nicotine SD but not the S Delta. These data provide additional evidence for sex differences in rats with the discriminative stimulus functions of nicotine under low, but not high, food-drive states-and may have implications for sex/gender differences in smoking cessation and relapse. Smoking cessation in women is more difficult than in men, and women often relapse. This study assessed nicotine sensitivity in male and female rats and found that females showed greater difficulty withholding from food-motivated behavior under the influence of nicotine-even when they were satiated and when food was unavailable. These results are consistent with what appears clinically.